Heterocyclic compounds configure a basic skeleton of a natural material, and among them, organic phosphorus compounds have pharmacological and physiological activities, such that the organic phosphorus compounds are important compounds in pharmaceutical, material, and crop protection agent fields.
Among them, since benzoxaphosphole oxide compounds have physiological activities and may be used as an important raw material or intermediate in agricultural and material chemistry fields in addition to being used in synthesizing a new medicine, an interest in synthesis methods thereof have increased. Therefore, synthesis methods of benzoxaphosphole oxide derivatives as described above have been reported (Chem. Rev. 2003, 103, 3029). Up to now, the methods of synthesizing benzoxaphosphole oxide have a disadvantage in that benzoxaphosphole oxide is synthesized through several steps.
Meanwhile, a dibenzoxaphosphorin oxide derivative is a lactone derivative including phosphorus. It was known that uses of lactone are various, and various application methods and synthesis methods have been reported (J. Org. Chem. 2007, 72, 9379-9382). In addition, it has been well known that lactone has physiological activities, and since lactone is used as a basic skeleton of a natural material, even in the case in which phosphorus is contained, it is expected that the lactone derivative will have physiological activities or be variously applied through additional steps. However, the number of reported compounds in which phosphorus is contained is small, and particularly, there is no reported compound in which various substituents are contained (Transition Met. Chem. 2008, 33, 505-510). In addition, recently, research into a method of synthesizing a carbon-carbon, carbon-nitrogen, or carbon-oxygen bond by using various transition metal catalysts through a carbon-hydrogen bond activation reaction with a directing group has been conducted. This reaction is characterized in that various bonds may be introduced by interaction between the catalyst and the directing group without pre-functionalization. Recently, it has been reported that various bonds are formed by using a directing group containing phosphorus through the carbon-hydrogen bond activation reaction with a transition metal (Org. Lett. 2013, 15, 3358-3361; Org. Lett. 2013, 15, 3986-3989). In addition, a method of forming a carbon-oxygen bond to synthesize a cyclic compound is a good method of synthesizing a novel heterocyclic compound (Org. Lett. 2013, 15, 5210-5213).
However, the case of synthesizing a benzoxaphosphole oxide derivative and a dibenzoxaphosphorin oxide derivative by using the transition metal catalyst through the carbon-hydrogen bond activation reaction has not yet been reported. Therefore, it is important to develop an efficient C—H bond activation reaction using a directing group associated with phosphorus.
The present invention relates to a new method of synthesizing a benzoxaphosphole oxide derivative and a dibenzoxaphosphorin oxide derivative having a short reaction step. The method of preparing a benzoxaphosphole oxide derivative and a dibenzoxaphosphorin oxide derivative according to the present invention has an advantage in that benzoxaphosphole oxide derivatives and dibenzoxaphosphorin oxide derivatives in which various substituents are introduced by an intramolecular carbon-oxygen coupling reaction due to the carbon (sp2 or sp3)-hydrogen bond activation reaction may be prepared from a phosphinic acid derivative in the presence of a palladium catalyst.